The ability to perform molecular and cellular analyses of biological systems has grown explosively over the past three decades. In particular, the advent and refinement of molecular and cellular techniques, such as DNA sequencing, gene cloning, monoclonal antibody production, cell transfection, amplification techniques (such as PCR), and transgenic animal formation, have fueled this explosive growth. These techniques have spawned an overwhelming number of identified genes, encoded proteins, engineered cell types, and assays for studying these genes, proteins, and cell types. As the number of possible combinations of samples, reagents, and assays becomes nearly incalculable, it has become increasingly apparent that novel approaches are necessary even to begin to make sense of this complexity, especially within reasonable temporal and monetary limitations.
One approach to these difficulties has been to reduce the scale of assays. Accordingly, substantial effort has been directed to developing assay methods and instrumentation for high-density microtiter plates. However, very small assay volumes in high-density microtiter plates, particularly assays with cells, may suffer from a number of shortcomings. For example, cells may be lost easily from wells, may be harmed by rapid fluid evaporation, may contaminate nearby wells, and may be difficult to remove efficiently from wells for additional analysis or culture. Thus, there is a need for systems that can effectively manipulate and analyze cells and other small particles, such as beads, in small volumes.